Nuclear magnetic resonance (NMR) techniques are finding increasing use in medical applications. NMR imaging, or magnetic resonance imaging (MRI) as it is sometimes known, has been found to be useful in the detection of a variety of diseases and disorders. MRI has several advantages over other imaging techniques. For example, unlike computerized tomographic methods, MRI does not employ ionizing radiation, and therefore is believed to be safer. Also, MRI can provide more information about soft tissue than can some other imaging methods.
The majority of the NMR techniques developed so far have been based on imaging of hydrogen nuclei. However, other nuclei offer potential advantages with respect to NMR. .sup.19 F in particular is of interest. The fluorine nucleus offers a strong NMR signal magnitude (high gyromagnetic ratio) close to that of protons. Virtually no imagable fluorine exists naturally in the human body, so essentially no background signal exists; any detectable signal comes only from whatever .sup.19 F has been administered to the subject.
.sup.19 F is a stable isotope and is naturally abundant, so there is no need for isotopic enrichment. Because its gyromagnetic ratio is about 94% that of hydrogen, existing equipment designed to image protons can be inexpensively adapted for .sup.19 F.
One important physiological parameter which might be assessed by means of .sup.19 F NMR is tissue oxygen tension (pO.sub.2). Oxygen is required for efficient function by most tissues; hypoxia leads to rapid cellular dysfunction and damage. In addition, tumor cells exhibit regional hypoxia, and their response to therapy is strongly dependent on the degree and extent of hypoxia. Tumors with very low pO.sub.2 exhibit marked resistance to radiotherapy. Many chemotherapeutic agents act preferentially on euoxic or hypoxic tissue. Thus, a reliable method of estimating tumor pO.sub.2 would be of significant help in treatment optimization for individual cancer patients.
Traditional techniques of measuring oxygen tension in tissue are generally invasive and sample localized volumes only, e.g., oxygen microelectrodes, mass spectrometer probes, or biopsy and cryospectrophotometry. Some noninvasive techniques which are available examine superficial tissues only, e.g. surface electrodes or fluorescence. Thus, the existing methods of measuring pO.sub.2 have significant problems and limitations.
The .sup.19 F NMR spin-lattice relaxation rate (R.sub.1 =1/T.sub.1) of perfluorocarbon emulsions is sensitive to oxygen tension. Therefore, .sup.19 F MRI has been used to map tissue pO.sub.2, but the data acquisition is slow (e.g., hours), in organs or tissue with low PFC concentrations, such as heart, brain, and tumor, and further tends to exhibit poor signal to noise ratios. .sup.19 F MRI requires specific observation of a single resonance, or the application of elaborate deconvolution, and thus only a single estimate of pO.sub.2 may be obtained.
Thus, a need exists for improved methods of measuring tissue oxygen tension. A non-invasive method that could measure pO.sub.2 in vivo accurately and rapidly could be significant in understanding the mechanisms of tissue function, and in planning and managing cancer therapy.